Insulin binding and action have been studied in cultured human fibroblasts. Cells are derived from controls, insulin resistant patients, anddiabetics. Activation of glycogen synthase and induction down-regulation, are being examined in these cells. Insulin receptor defects have been found on approximately half of the cell lines from insulin resistant patients. These include defects in receptor number, receptor affinity, and pH optimum of binding. Post-receptor defects, in the presence of normal insulin receptors, are also present in some cells from insulin resistant patients. Cells from Type I diabetics are normal in most respects.